作者: Yang, Xiaolin ; Hu, Tianyu ; Xiong, Zhiqi ; Sun, Shan ; Yang, Xiaobao ; Liu, Fengjiang ; Rao, Zihe ; Yang, Xiuna ; Liang, Jingxi ; Yang, Haitao ; Zhang, Bing ; Wang, Haofeng ; Guddat, Luke W

New anti-tubercular agents are urgently needed to address the emerging threat of drug resistance to human tuberculosis. Here, we have used structure-assisted methods to develop compounds that target mycobacterial membrane protein large 3 (MmpL3). MmpL3 is essential for the transport of mycolic acids, an important cell-wall component of mycobacteria. We prepared compounds that potently inhibit the growth of Mycobacterium tuberculosis (Mtb) and other mycobacteria in cell culture. The cryoelectron microscopy (cryo-EM) structure of mycobacterial MmpL3 in complex with one of these compounds (ST004) was determined using lipid nanodiscs at an overall resolution of 3.36 Å. The structure reveals the binding mode of ST004 to MmpL3, with the S4 and S5 subsites of the inhibitor-binding pocket in the proton translocation channel playing vital roles. These data are a promising starting point for the development of anti-tuberculosis drugs that target MmpL3.

2021-12-01·Ying yong sheng tai xue bao = The journal of applied ecology

秸秆还田条件下盐渍土团聚体中有机碳化学结构特征.

Article

作者: Zhang, Yue-Xian ; Wen, Xin ; Hong, Mei ; Zhao, Hui-Xin ; Xing, An ; Shen, Qin-Guo ; Pei, Zhi-Fu

为揭示秸秆还田后盐渍土团聚体中有机碳分布规律和化学结构特征,本研究以苏打碱化潮土为对象,于2020年设置0(CK)、2100(ST₁)、4200(ST₂)、6300(ST₃)、8400(ST₄)和10500 kg·hm^-2(全量还田,ST₅)6个不同秸秆还田用量处理,通过物理分组方法并结合红外光谱技术,测定土壤各粒级团聚体及内部不同组分有机碳含量和红外光谱特征。结果表明: 1)随着秸秆还田量增加,土壤及各级团聚体有机碳含量均呈增加趋势。2)不同秸秆还田处理均显著提高了53～250 μm团聚体轻组有机碳(LOC)含量;与CK相比,ST₃、ST₄处理显著提高250～2000 μm团聚体中矿物结合有机碳(MOC)和53～250 μm团聚体中细颗粒有机碳(fPOC)含量;团聚体内部不同组分有机碳含量由高到低均表现为: LOC>MOC>POC;250～2000 μm团聚体内部fPOC含量高于粗颗粒有机碳(cPOC)含量。3)主成分分析结果显示,秸秆还田对团聚体不同组分有机碳化学结构的影响较小,有机碳化学结构差异主要受粒级的影响。4)>250 μm粒级团聚体有机碳主要来源于芳香碳和多糖,53～250 μm粒级团聚体有机碳主要来源于单糖和多糖等碳水化合物,<53 μm黏粒有机碳主要来源于脂肪碳、烷基碳、芳香碳和酚醇化合物;不同粒级团聚体内部LOC主要来源于脂肪碳、芳香碳、酚醇化合物,颗粒有机碳(POC)主要来源于碳水化合物,MOC主要来源于烷基碳。综上,秸秆还田短期内能够提高土壤团聚体有机碳含量,但对团聚体有机碳化学结构无显著影响,且不同团聚体内部相同粒级组分有机碳化学结构相似,随着粒径减小,有机碳含量增加,化学结构趋于稳定。因此,秸秆还田短期内可促进盐渍土团聚体对有机碳的固定,但不改变有机碳化学结构特征,同时,土壤有机碳在团聚体中的存在位置和受保护程度是影响有机碳化学结构的主要因素。.

2021-11-01·International Journal of Biological Macromolecules1区 · 化学

Granzyme B and perforin produced by SEC2 mutant-activated human CD4+ T cells and CD8+ T cells induce apoptosis of K562 leukemic cells by the mitochondrial apoptotic pathway

1区 · 化学

Article

作者: Zhang, Guojun ; Jiang, Fengli ; Wu, Tianyi ; Zheng, Guoliang ; Wu, Lizhao

Staphylococcal enterotoxin C2 (SEC2), a classical representative of superantigens, activates T cells that produce massive cytokines. This characteristic makes SEC2 a promising candidate drug for cancer immunotherapy. Previous study showed that ST-4, a SEC2 mutant, enhanced recognition of mouse T-cell receptor Vβ regions, and activated the increased number of T cells that produced more cytokines. However, the underlying molecular mechanism for stimulation of human peripheral blood mononuclear cells (PBMCs) and antitumor effect on human tumor cells remains unknown. Herein, we showed that ST-4 significantly activated TCR Vβ 12, 13A, 14, 15, 17, and 20 CD4⁺ and CD8⁺ T cells, which produced substantial amounts of granzyme B and perforin. These cytokines exhibited antitumor effect on K562 cells by promoting apoptosis and inducing S-phase cell cycle arrest. Conversely, the granzyme B inhibitor or perforin inhibitor significantly weakened antitumor effect of ST-4, accompanied by a decrease of cleaved proapoptotic BAX and cytochrome c, and an increase of antiapoptotic BCL2. Taken together, these data suggest that granzyme B and perforin produced by ST-4-activated CD4⁺ T cells and CD8⁺ T cells play a pivotal role in inducing K562 cell apoptosis by the mitochondrial apoptotic pathway, and support ST-4 as a potential candidate for cancer immunotherapy.

100 项与 ST-004 相关的药物交易

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